Pathophysiologie des rechten Ventrikels und seine pulmonal-vaskuläre Interaktion

Khodr Tello; Nils Kremer; Andreas J. Rieth; Olympia Bikou; Julian Müller; Regina Steringer-Mascherbauer; Stephan Holt; Norbert Weissmann; Ralph T. Schermuly; Wolfgang M. Kuebler

doi:10.1055/a-2625-4753

Pneumologie, Table of Contents

Pneumologie 2025; 79(10): 712-722
DOI: 10.1055/a-2625-4753

Übersicht

Pathophysiologie des rechten Ventrikels und seine pulmonal-vaskuläre Interaktion

Pathophysiology of the Right Ventricle and its Pulmonary Vascular Interaction

Authors

Khodr Tello^*

¹Medizinische Klinik und Poliklinik II, Justus-Liebig-Universität Gießen, Universitätsklinikum Gießen-Marburg, Mitglied des Deutschen Zentrums für Lungenforschung, Gießen, Deutschland
Nils Kremer^*

¹Medizinische Klinik und Poliklinik II, Justus-Liebig-Universität Gießen, Universitätsklinikum Gießen-Marburg, Mitglied des Deutschen Zentrums für Lungenforschung, Gießen, Deutschland
Andreas J. Rieth

²Abteilung für Kardiologie, Kerckhoff-Klinik Bad Nauheim, Bad Nauheim, Deutschland
Olympia Bikou

³Medizinische Klinik und Poliklinik I, LMU Klinikum, LMU München, Münschen, Deutschland
Julian Müller

⁴Klinik für Pneumologie, Universitätsspital Zürich, Zürich, Schweiz
Regina Steringer-Mascherbauer

⁵Interne 2, Ordensklinikum Linz, Linz, Österreich
Stephan Holt

⁶kardiologische/pneumologische Praxis am Steintor, Recklinghausen, Deutschland
Norbert Weissmann

¹Medizinische Klinik und Poliklinik II, Justus-Liebig-Universität Gießen, Universitätsklinikum Gießen-Marburg, Mitglied des Deutschen Zentrums für Lungenforschung, Gießen, Deutschland
Ralph T. Schermuly

¹Medizinische Klinik und Poliklinik II, Justus-Liebig-Universität Gießen, Universitätsklinikum Gießen-Marburg, Mitglied des Deutschen Zentrums für Lungenforschung, Gießen, Deutschland
Wolfgang M. Kuebler

⁷Institut für Physiologie, Charité – Universitätsmedizin Berlin, Berlin, Deutschland

Abstract

Zusammenfassung

Dieser Kommentar zum WSPH-Statement 2024 wurde von Expert*innen des deutschsprachigen Raumes verfasst. Schwerpunkte sind die aktuelle Definition der Rechtsherzinsuffizienz und ihre Abbildung durch RV-PA-Kopplungsparameter; pathomechanistische Fortschritte zu Entzündung, Fibrose, metabolischer Dysfunktion und geschlechtsspezifischen Hormoneinflüssen; die Rolle des rechten Vorhofs als Frühmarker der RV-Belastung; Kriterien für adaptive versus maladaptive RV-Remodellierung mit invasiven und nicht-invasiven Messgrößen; Auswirkungen neuer Therapien – insbesondere des Activin-Fallenproteins Sotatercept – auf Hämodynamik und RV-Struktur; der translationale Wert großer Tiermodelle sowie praxisnahe Konsequenzen für multiparametrische Bildgebung. Insgesamt soll diese Kommentierung zeigen, wie sich diese Erkenntnisse in alltagsrelevante Diagnose- und Monitoringstrategien überführen lassen.

Abstract

Authored by a consortium of experts from the German-speaking countries, this commentary on the 2024 World Symposium on Pulmonary Hypertension (WSPH) statement spotlights the updated definition of right-heart failure and its quantification through right-ventricular–pulmonary-artery (RV–PA) coupling indices. It reviews mechanistic advances in inflammation, fibrosis, metabolic dysregulation and sex-hormone modulation; elevates the right atrium as an early sentinel of RV load; refines criteria distinguishing adaptive from maladaptive RV remodelling using both invasive and non-invasive metrics; and analyses the haemodynamic and structural impact of emerging therapies – notably the activin-trap sotatercept – on the RV; the translational value of large-animal models and practical implications for multiparametric imaging. Overall, the commentary seeks to demonstrate how these insights can be integrated into routine diagnostic and monitoring strategies.

Schlüsselwörter

Rechtsherzinsuffizienz - rechtsventrikuläre pulmonalarterielle Kopplung - Maladaptation

Keywords

right heart insufficiency - right ventricular pulmonary arterial coupling - maladaptation

Full Text

References

Literatur
1 Noordegraaf AV, Chin KM, Haddad F. et al. Pathophysiology of the right ventricle and of the pulmonary circulation in pulmonary hypertension: an update. Eur Respir J 2019; 53: 1801900
2 Sanz J, Sánchez-Quintana D, Bossone E. et al. Anatomy, Function, and Dysfunction of the Right Ventricle: JACC State-of-the-Art Review. J Am Coll Cardiol 2019; 73: 1463-1482
3 Richter MJ, Peters D, Ghofrani HA. et al. Evaluation and Prognostic Relevance of Right Ventricular-Arterial Coupling in Pulmonary Hypertension. Am J Respir Crit Care Med 2020; 201: 116-119
4 Yogeswaran A, Petermann R, Kremer NC. et al. Right Ventricular – Pulmonary Arterial Coupling Predicts Mortality in Precapillary Pulmonary Hypertension. ERJ Open Research 2025; 11: 00685-2024
5 Ghofrani H-A, Gomberg-Maitland M, Zhao L. et al. Mechanisms and treatment of pulmonary arterial hypertension. Nat Rev Cardiol 2025; 22: 105-120
6 Vizza CD, Lang IM, Badagliacca R. et al. Aggressive Afterload Lowering to Improve the Right Ventricle: A New Target for Medical Therapy in Pulmonary Arterial Hypertension?. Am J Respir Crit Care Med 2022; 205: 751-760
7 Leopold JA, Kawut SM, Aldred MA. et al. Diagnosis and Treatment of Right Heart Failure in Pulmonary Vascular Diseases: A National Heart, Lung, and Blood Institute Workshop. Circ Heart Fail 2021; 14: e007975
8 Rako ZA, Kremer N, Yogeswaran A. et al. Adaptive versus maladaptive right ventricular remodelling. ESC Heart Failure 2023; 10: 762-775
9 Tello K, Wan J, Dalmer A. et al. Validation of the Tricuspid Annular Plane Systolic Excursion/Systolic Pulmonary Artery Pressure Ratio for the Assessment of Right Ventricular-Arterial Coupling in Severe Pulmonary Hypertension. Circ Cardiovasc Imaging 2019; 12: e009047
10 Sanz J, Sánchez-Quintana D, Bossone E. et al. Anatomy, Function, and Dysfunction of the Right Ventricle: JACC State-of-the-Art Review. J Am Coll Cardiol 2019; 73: 1463-1482
11 Rudski LG, Lai WW, Afilalo J. et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr 2010; 23: 685-713 quiz 786–788
12 Humbert M, Kovacs G, Hoeper MM. et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: Developed by the task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS). Endorsed by the International Society for Heart and Lung Transplantation (ISHLT) and the European Reference Network on rare respiratory diseases (ERN-LUNG). European Heart Journal 2022; 43: 3618-3731
13 Golbin JM, Shukla N, Nero N. et al. Non-invasive surrogates for right Ventricular-Pulmonary arterial coupling: a systematic review and Meta-Analysis. Pulm Circ 2024; 14: e70004
14 Zhan Y, Friedrich MG, Dendukuri N. et al. Meta-Analysis of Normal Reference Values for Right and Left Ventricular Quantification by Cardiovascular Magnetic Resonance. Circ Cardiovasc Imaging 2024; 17: e016090
15 Lewis RA, Johns CS, Cogliano M. et al. Identification of Cardiac Magnetic Resonance Imaging Thresholds for Risk Stratification in Pulmonary Arterial Hypertension. Am J Respir Crit Care Med 2020; 201: 458-468
16 Park JF, Clark VR, Banerjee S. et al. Transcriptomic Analysis of Right Ventricular Remodeling in Two Rat Models of Pulmonary Hypertension. Circ Heart Fail 2021; 14: e007058
17 Prisco SZ, Hartweck LM, Rose L. et al. Inflammatory Glycoprotein 130 Signaling Links Changes in Microtubules and Junctophilin-2 to Altered Mitochondrial Metabolism and Right Ventricular Contractility. Circ Heart Fail 2022; 15: e008574
18 Al-Qazazi R, Lima PDA, Prisco SZ. et al. Macrophage – NLRP3 Activation Promotes Right Ventricle Failure in Pulmonary Arterial Hypertension. Am J Respir Crit Care Med 2022; 206: 608-624
19 Vang A, da Silva Gonçalves Bos D, Fernandez-Nicolas A. et al. α7 Nicotinic acetylcholine receptor mediates right ventricular fibrosis and diastolic dysfunction in pulmonary hypertension. JCI Insight 2021; 6
20 Hirsch K, Nolley S, Ralph DD. et al. Circulating markers of inflammation and angiogenesis and clinical outcomes across subtypes of pulmonary arterial hypertension. J Heart Lung Transplant 2023; 42: 173-182
21 Prins KW, Archer SL, Pritzker M. et al. Interleukin-6 is independently associated with right ventricular function in pulmonary arterial hypertension. J Heart Lung Transplant 2018; 37: 376-384
22 Jasiewicz M, Knapp M, Waszkiewicz E. et al. Enhanced IL-6 trans-signaling in pulmonary arterial hypertension and its potential role in disease-related systemic damage. Cytokine 2015; 76: 187-192
23 Salazar IMC, Lancaster AC, Jani VP. et al. Poor cardiac output reserve in pulmonary arterial hypertension is associated with right ventricular stiffness and impaired interventricular dependence. Eur Respir J 2024; 64: 2400420
24 Talati M, Hemnes A. Fatty acid metabolism in pulmonary arterial hypertension: role in right ventricular dysfunction and hypertrophy. Pulm Circ 2015; 5: 269-278
25 Koop AC, Bossers GPL, Ploegstra M. et al. Metabolic Remodeling in the Pressure‐Loaded Right Ventricle: Shifts in Glucose and Fatty Acid Metabolism – A Systematic Review and Meta‐Analysis. J Am Heart Assoc 2019; 8: e012086
26 Prisco SZ, Eklund M, Moutsoglou DM. et al. Intermittent Fasting Enhances Right Ventricular Function in Preclinical Pulmonary Arterial Hypertension. J Am Heart Assoc 2021; 10: e022722
27 Agrawal V, Hemnes AR, Shelburne NJ. et al. l‐Carnitine therapy improves right heart dysfunction through Cpt1‐dependent fatty acid oxidation. Pulm Circ 2022; 12: e12107
28 Prisco SZ, Eklund M, Raveendran R. et al. With No Lysine Kinase 1 Promotes Metabolic Derangements and RV Dysfunction in Pulmonary Arterial Hypertension. JACC Basic Transl Sci 2021; 6: 834-850
29 Kazmirczak F, Hartweck LM, Vogel NT. et al. Intermittent Fasting Activates AMP-Kinase to Restructure Right Ventricular Lipid Metabolism and Microtubules. JACC Basic Transl Sci 2023; 8: 239-254
30 Han Y, Forfia P, Vaidya A. et al. Ranolazine Improves Right Ventricular Function in Patients With Precapillary Pulmonary Hypertension: Results From a Double-Blind, Randomized, Placebo-Controlled Trial. J Card Fail 2021; 27: 253-257
31 McNair BD, Polson SM, Shorthill SK. et al. Metformin protects against pulmonary hypertension-induced right ventricular dysfunction in an age- and sex-specific manner independent of cardiac AMPK. Am J Physiol Heart Circ Physiol 2023; 325: H278-H292
32 Dignam JP, Sharma S, Stasinopoulos I. et al. Pulmonary arterial hypertension: Sex matters. Br J Pharmacol 2024; 181: 938-966
33 Mair KM, Johansen AKZ, Wright AF. et al. Pulmonary arterial hypertension: basis of sex differences in incidence and treatment response. Br J Pharmacol 2014; 171: 567-579
34 Ventetuolo CE, Moutchia J, Baird GL. et al. Baseline Sex Differences in Pulmonary Arterial Hypertension Randomized Clinical Trials. Annals ATS 2023; 20: 58-66
35 DesJardin JT, Kime N, Kolaitis NA. et al. Investigating the “sex paradox” in pulmonary arterial hypertension: Results from the Pulmonary Hypertension Association Registry (PHAR). J Heart Lung Transplant 2024; 43: 901-910
36 Walsh TP, Baird GL, Atalay MK. et al. Experimental design of the Effects of Dehydroepiandrosterone in Pulmonary Hypertension (EDIPHY) trial. Pulm Circ 2021; 11 2045894021989554
37 Ventetuolo C. Effects of DHEA in Pulmonary Hypertension (DiPH).
38 Lahm T. Sex differences in pulmonary hypertension: are we cleaning up the mess?. Eur Respir J 2016; 47: 390-393
39 Cheng T-C, Philip JL, Tabima DM. et al. Estrogen receptor-α prevents right ventricular diastolic dysfunction and fibrosis in female rats. Am J Physiol Heart Circ Physiol 2020; 319: H1459-H1473
40 Frump AL, Albrecht M, Yakubov B. et al. 17β-Estradiol and estrogen receptor α protect right ventricular function in pulmonary hypertension via BMPR2 and apelin. J Clin Invest 2021; 131: e129433 129433
41 Tello K, Richter MJ, Yogeswaran A. et al. Sex Differences in Right Ventricular-Pulmonary Arterial Coupling in Pulmonary Arterial Hypertension. Am J Respir Crit Care Med 2020; 202: 1042-1046
42 Singh I, Oliveira RKF, Heerdt PM. et al. Sex-Related Differences in Dynamic Right Ventricular-Pulmonary Vascular Coupling in Heart Failure With Preserved Ejection Fraction. Chest 2021; 159: 2402-2416
43 Marcus JT, Westerhof BE, Groeneveldt JA. et al. Vena cava backflow and right ventricular stiffness in pulmonary arterial hypertension. Eur Respir J 2019; 54: 1900625
44 Wessels JN, Mouratoglou SA, Van Wezenbeek J. et al. Right atrial function is associated with right venticular diastolic stiffness: RA–RV interaction in pulmonary arterial hypertension. Eur Respir J 2022; 59: 2101454
45 Wessels JN, van Wezenbeek J, de Rover J. et al. Right Atrial Adaptation to Precapillary Pulmonary Hypertension. JACC 2023; 82: 704-717
46 Jiang H, Salmon RM, Upton PD. et al. The Prodomain-bound Form of Bone Morphogenetic Protein 10 Is Biologically Active on Endothelial Cells. J Biol Chem 2016; 291: 2954-2966
47 Goetze JP, Bruneau BG, Ramos HR. et al. Cardiac natriuretic peptides. Nat Rev Cardiol 2020; 17: 698-717
48 Richter MJ, Fortuni F, Alenezi F. et al. Imaging the right atrium in pulmonary hypertension: A systematic review and meta-analysis. J Heart Lung Transplant 2023; 42: 433-446
49 Richter MJ, Zedler D, Berliner D. et al. Clinical Relevance of Right Atrial Functional Response to Treatment in Pulmonary Arterial Hypertension. Front Cardiovasc Med 2021; 8: 775039
50 Tello K, Dalmer A, Vanderpool R. et al. Right ventricular function correlates of right atrial strain in pulmonary hypertension: a combined cardiac magnetic resonance and conductance catheter study. Am J Physiol Heart Circ Physiol 2020; 318: H156-H164
51 Richter MJ, Fortuni F, Wiegand MA. et al. Association of right atrial conduit phase with right ventricular lusitropic function in pulmonary hypertension. Int J Cardiovasc Imaging 2020; 36: 633-642
52 Nemes A, Kormányos Á, Domsik P. et al. Normal reference values of right atrial strain parameters using three-dimensional speckle-tracking echocardiography (results from the MAGYAR-Healthy Study). Int J Cardiovasc Imaging 2019; 35: 2009-2018
53 Krittanawong C, Maitra NS, Hassan VHU. et al. Normal Ranges of Right Atrial Strain. JACC Cardiovasc Imaging 2023; 16: 282-294
54 Querejeta RocaG, Campbell P, Claggett B. et al. Right Atrial Function in Pulmonary Arterial Hypertension. Circ Cardiovasc Imaging 2015; 8: e003521 discussion e003521
55 Keranov S, Dörr O, Jafari L. et al. CILP1 as a biomarker for right ventricular maladaptation in pulmonary hypertension. Eur Respir J 2021; 57: 1901192
56 Zelt JGE, Cadete V, Deng Y. et al. Right Ventricular Maladaptation to Pressure Overload in Fischer Rats Is Associated With Profound Deficiency in Adenylate Kinase 1 and Impaired Ventricular Energetics. Hypertension 2022; 79: 2774-2786
57 Humbert M, McLaughlin V, Gibbs JSR. et al. Sotatercept for the Treatment of Pulmonary Arterial Hypertension. N Engl J Med 2021; 384: 1204-1215
58 Hoeper MM, Badesch DB, Ghofrani HA. et al. Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension. N Engl J Med 2023; 388: 1478-1490
59 Souza R, Badesch DB, Ghofrani HA. et al. Effects of sotatercept on haemodynamics and right heart function: analysis of the STELLAR trial. Eur Respir J 2023; 62: 2301107
60 Waxman AB, Systrom DM, Manimaran S. et al. SPECTRA Phase 2b Study: Impact of Sotatercept on Exercise Tolerance and Right Ventricular Function in Pulmonary Arterial Hypertension. Circ Heart Fail 2024; 17: e011227
61 Zakrzewicz A, Kouri FM, Nejman B. et al. The transforming growth factor-β/Smad2,3 signalling axis is impaired in experimental pulmonary hypertension. Eur Respir J 2007; 29: 1094-1104
62 Zabini D, Granton E, Hu Y. et al. Loss of SMAD3 Promotes Vascular Remodeling in Pulmonary Arterial Hypertension via MRTF Disinhibition. Am J Respir Crit Care Med 2018; 197: 244-260
63 Cuthbertson I, Morrell NW, Caruso P. BMPR2 Mutation and Metabolic Reprogramming in Pulmonary Arterial Hypertension. Circ Res 2023; 132: 109-126
64 Humbert M, McLaughlin VV, Badesch DB. et al. Sotatercept in Patients with Pulmonary Arterial Hypertension at High Risk for Death. N Engl J Med 2025; 392: 1987-2000
65 Guihaire J, Haddad F, Noly P-E. et al. Right ventricular reserve in a piglet model of chronic pulmonary hypertension. Eur Respir J 2015; 45: 709-717
66 Ukita R, Stokes JW, Wu WK. et al. A Large Animal Model for Pulmonary Hypertension and Right Ventricular Failure: Left Pulmonary Artery Ligation and Progressive Main Pulmonary Artery Banding in Sheep. J Vis Exp 2021; (173): e62694
67 Bikou O, Ishikawa K, Fish KM. et al. Modeling Pulmonary Hypertension: A Pig Model of Postcapillary Pulmonary Hypertension. Methods Mol Biol 2018; 1816: 367-383
68 Aguero J, Hammoudi N, Bikou O. et al. Chronic Pulmonary Artery Embolization Models in Large Animals. Methods Mol Biol 2018; 1816: 353-366
69 Boucherat O, Agrawal V, Lawrie A. et al. The Latest in Animal Models of Pulmonary Hypertension and Right Ventricular Failure. Circ Res 2022; 130: 1466-1486
70 Tello K, Dalmer A, Vanderpool R. et al. Cardiac Magnetic Resonance Imaging-Based Right Ventricular Strain Analysis for Assessment of Coupling and Diastolic Function in Pulmonary Hypertension. JACC Cardiovasc Imaging 2019; 12: 2155-2164
71 Yoshida K, van Wezenbeek J, Wessels JN. et al. Tricuspid regurgitation in pulmonary arterial hypertension: a right ventricular volumetric and functional analysis. Eur Respir J 2024; 63: 2301696
72 Yoshida K, Axelsen JB, Saku K. et al. How to incorporate tricuspid regurgitation in right ventricular-pulmonary arterial coupling. J Appl Physiol (1985) 2023; 135: 53-59
73 Tamborini G, Muratori M, Brusoni D. et al. Is right ventricular systolic function reduced after cardiac surgery? A two- and three-dimensional echocardiographic study. Eur J Echocardiogr 2009; 10: 630-634
74 Kremer N, Roller FC, Kremer S. et al. Native hepatic T1-time as a non-invasive predictor of diastolic dysfunction and a monitoring tool for disease progression and treatment response in patients with pulmonary hypertension. Int J Cardiol 2024; 409: 132189
75 Rako ZA, Yogeswaran A, Yildiz S. et al. Liver stiffness is associated with right heart dysfunction, cardiohepatic syndrome, and prognosis in pulmonary hypertension. J Heart Lung Transplant 2024; 43: 1105-1115
76 Yogeswaran A, Rako ZA, Yildiz S. et al. Echocardiographic evaluation of right ventricular diastolic function in pulmonary hypertension. ERJ Open Research 2023; 9: 00226-2023
77 Kremer N, Rako Z, Glocker F. et al. Monitoring of Right Ventricular Failure With Daily Pressure Volume Loops Obtained via an Application and 3-Dimensional Echocardiography. Circ Heart Fail 2023; 16: e010097
78 Kremer N, Glocker F, Schäfer S. et al. Precision cardiac monitoring: algorithmic real-time assessment of right ventricular function in pulmonary hypertension. ESC Heart Fail 2024; 11: 2469-2472
79 Addetia K, Miyoshi T, Amuthan V. et al. Normal Values of Three-Dimensional Right Ventricular Size and Function Measurements: Results of the World Alliance Societies of Echocardiography Study. J Am Soc Echocardiogr 2023; 36: 858-866.e1
80 Carvalho Singulane C, Singh A, Miyoshi T. et al. Sex-, Age-, and Race-Related Normal Values of Right Ventricular Diastolic Function Parameters: Data from the World Alliance Societies of Echocardiography Study. J Am Soc Echocardiogr 2022; 35: 426-434
81 Soulat-Dufour L, Addetia K, Miyoshi T. et al. Normal Values of Right Atrial Size and Function According to Age, Sex, and Ethnicity: Results of the World Alliance Societies of Echocardiography Study. J Am Soc Echocardiogr 2021; 34: 286-300
82 Lewis RA, Johns CS, Cogliano M. et al. Identification of Cardiac Magnetic Resonance Imaging Thresholds for Risk Stratification in Pulmonary Arterial Hypertension. Am J Respir Crit Care Med 2020; 201: 458-468
83 Ghio S, Mercurio V, Fortuni F. et al. A comprehensive echocardiographic method for risk stratification in pulmonary arterial hypertension. Eur Respir J 2020; 56: 2000513
84 Fine NM, Chen L, Bastiansen PM. et al. Outcome prediction by quantitative right ventricular function assessment in 575 subjects evaluated for pulmonary hypertension. Circ Cardiovasc Imaging 2013; 6: 711-721
85 El-Kersh K, Zhao C, Elliott G. et al. Derivation of a Risk Score (REVEAL-ECHO) Based on Echocardiographic Parameters of Patients With Pulmonary Arterial Hypertension. Chest 2023; 163: 1232-1244
86 Fine NM, Chen L, Bastiansen PM. et al. Outcome prediction by quantitative right ventricular function assessment in 575 subjects evaluated for pulmonary hypertension. Circ Cardiovasc Imaging 2013; 6: 711-721
87 Alabed S, Shahin Y, Garg P. et al. Cardiac-MRI Predicts Clinical Worsening and Mortality in Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis. JACC Cardiovasc Imaging 2021; 14: 931-942
88 Alabed S, Garg P, Alandejani F. et al. Establishing minimally important differences for cardiac MRI end-points in pulmonary arterial hypertension. Eur Respir J 2023; 62: 2202225
89 Vonk Noordegraaf A, Channick R, Cottreel E. et al. The REPAIR Study: Effects of Macitentan on RV Structure and Function in Pulmonary Arterial Hypertension. JACC Cardiovasc Imaging 2022; 15: 240-253
90 Badagliacca R, Poscia R, Pezzuto B. et al. Prognostic relevance of right heart reverse remodeling in idiopathic pulmonary arterial hypertension. J Heart Lung Transplant 2017; S1053-2498(17)32041-7
91 Badagliacca R, Raina A, Ghio S. et al. Influence of various therapeutic strategies on right ventricular morphology, function and hemodynamics in pulmonary arterial hypertension. J Heart Lung Transplant 2018; 37: 365-375
92 Badagliacca R, Papa S, Manzi G. et al. Usefulness of Adding Echocardiography of the Right Heart to Risk-Assessment Scores in Prostanoid-Treated Pulmonary Arterial Hypertension. JACC Cardiovasc Imaging 2020; 13: 2054-2056
93 D’Alonzo GE, Barst RJ, Ayres SM. et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med 1991; 115: 343-349
94 van Wolferen SA, van de Veerdonk MC, Mauritz G-J. et al. Clinically significant change in stroke volume in pulmonary hypertension. Chest 2011; 139: 1003-1009
95 Brittain EL, Niswender K, Agrawal V. et al. Mechanistic Phase II Clinical Trial of Metformin in Pulmonary Arterial Hypertension. J Am Heart Assoc 2020; 9: e018349
96 Lurz P, Orban M, Besler C. et al. Clinical characteristics, diagnosis, and risk stratification of pulmonary hypertension in severe tricuspid regurgitation and implications for transcatheter tricuspid valve repair. Eur Heart J 2020; 41: 2785-2795
97 Kassis N, Layoun H, Goyal A. et al. Mechanistic Insights into Tricuspid Regurgitation Secondary to Pulmonary Arterial Hypertension. Am J Cardiol 2022; 175: 97-105